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What is the mechanism for the synthesis of ibuprofen from 2-methylpropylbenzene and carbon dioxide, and what are the key factors that influence the yield and purity of the final product?

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The synthesis of ibuprofen from 2-methylpropylbenzene  isobutylbenzene  and carbon dioxide involves several steps. The overall process is known as the Boots synthesis, which was developed by the Boots Company in the 1960s. Here is the mechanism for the synthesis:1. Friedel-Crafts acylation: The first step involves the Friedel-Crafts acylation of 2-methylpropylbenzene with acetyl chloride in the presence of a Lewis acid catalyst, such as aluminum chloride  AlCl3 . This reaction forms a ketone, 2- 4-isobutylphenyl propanone.2. Reduction of the ketone: The ketone formed in the previous step is reduced to an alcohol using a reducing agent, such as sodium borohydride  NaBH4  or lithium aluminum hydride  LiAlH4 . This results in the formation of 2- 4-isobutylphenyl propanol.3. Carboxylation: The alcohol is then reacted with carbon dioxide  CO2  under high pressure and temperature in the presence of a base, such as sodium hydroxide  NaOH . This step forms the carboxylic acid, 2- 4-isobutylphenyl propionic acid, which is the final product, ibuprofen.Key factors that influence the yield and purity of the final product include:1. Reaction conditions: The temperature, pressure, and reaction time can significantly impact the yield and purity of the product. For example, the carboxylation step requires high pressure and temperature for optimal results.2. Choice of catalysts and reagents: The choice of catalysts and reagents can also affect the yield and purity. For instance, using a more selective catalyst in the Friedel-Crafts acylation can help minimize side reactions and improve the yield.3. Purification techniques: The efficiency of purification techniques, such as recrystallization, chromatography, or distillation, can impact the purity of the final product. Proper selection and optimization of these techniques are essential for obtaining high-purity ibuprofen.4. Control of side reactions: Side reactions can lead to the formation of impurities and by-products, which can reduce the yield and purity of the final product. Monitoring and controlling these side reactions are crucial for improving the overall synthesis process.
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